Non-insulin dependent diabetes mellitus is a common chronic disease that develops in most populations in late middle age. The Pima Indians of Arizona have the highest reported prevalence of this disease in the world and in contrast to many populations the disease often presents at an earlier age. As a result of long-term epidemiological studies in the total population, the familial nature of the disease has been well documented, and segregation analyses suggest the possibility of inheritance by a single additive major gene. This project will search for genetic determinants of NIDDM using the techniques of genetic linkage analysis with genetic markers to identify the chromosomal location of inherited determinants of NIDDM in the Pima Indian population. A number of informative pedigrees have been identified and lymphoblast cell lines from informative members of these pedigrees established. DNA from these lymphoblasts is isolated and polymorphic probes applied to search for evidence of linkage of these markers and NIDDM. Probes with established chromosomal locations will be used to screen the genome to detect genetic linkage with NIDDM as described in Project# Z01 DK 69045-01 (Molecular genetic analysis of a chromosome 4 region harboring agent controlling insulin action). The power to detect linkage was estimated under several sets of assumptions about mode of inheritance of diabetes and informativeness and location of DNA markers. With a large number of sib-pairs and highly polymorphic markers, the power to detect a major diabetes-susceptibility gene in the Pima is high.